Improvement of IVF outcome in poor responders by discontinuation of GnRH analogue during the gonadotropin stimulation phase - A function of improved embryo quality

Purpose: To assess the efficacy of a protocol involving the discontinuation of the GnRH analogue at the mid-phase of ovarian stimulation for NF in pat ients with a previous poor response Methods: Prospective case-control evaluation compared with same patient's p revious performance. Thirty-six patients enrolled in an IVF program were tr eated in two consecutive cycles. The first with a standardized protocol uti lizing mid-luteal administration of Nafarelin (N) 600 mcg/d continued throu ghout the stimulation phase with human menopausal gonadotropin (hMG) until follicles of 20 mm were identified by transvaginal ultrasound (Standard gro up). Patients with a poor response in the Standard cycle were treated in th e subsequent cycle with N and hMG initially in a similar manner then N was stopped after 5 days of hMG stimulation (N-stop group). All clinical and la boratory aspects of treatment were done in a similar fashion in both cycles , each patient acting as her own control Results: Results were analyzed by paired t test. The change in each paramet er in the N-stop cycle was expressed as the percent change as compared with the standard protocol cycle for each patient. Peak estradiol (E2) and numb er of aspirated oocytes were increased in the N-stop cycle (+16.9% and +28% , respectively), but insignificantly so. The percent of cleaving embryos wa s significantly increased by 27.9% (p = 0.03) in the N-stop cycle, as embry o morphology was improved by 22% (p = 002). The efficacy of gonadotropin tr eatment was enhanced in the N-stop cycle, as expressed by a 32.5 % increase in oocytes retrieved per hMG ampoule administered (p = 0.04). Three cycles of 36 were cancelled during the N-stop cycle, whereas only one was cancell ed in the standard protocol cycle. Of the 36 patients 7 conceived in the N- stop protocol and 5 are ongoing pregnancies Conclusion: Discontinuation of GnRH-a during ovarian stimulation for NF has a beneficial, bur not statistically significant, effect on both E2 and ooc yte production. Embryo cleavage razes and morphology were significantly imp roved, this may be due to improved oocyte quality, which may have been resp onsible for achieving pregnancies. The efficacy of gonadotropin treatment w as enhanced when GnRH-a was discontinued These results hint that GnRH-a may have a direct negative effect on folliculogenesis and oocytes, which is ap parent especially in poor responder patients.